A transcriptional switch in a novel non-canonical, ßcatenin dependent Wnt pathway controls axon midline decisions
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA551612 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9610920.fastq.gz | Fastqsanger.gz | |||
| SRR9610921.fastq.gz | Fastqsanger.gz | |||
| SRR9610922.fastq.gz | Fastqsanger.gz | |||
| SRR9610923.fastq.gz | Fastqsanger.gz | |||
| SRR9610924.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:During the establishment of neuronal connections, axons must correctly navigate long pathways to find their targets. By focusing on the guidance of visual axons at the midline, we describe for the first time that a switch in a novel branch of the Wnt pathway, which is not the canonical or the non-canonical, that controls axonal directionality. This finding conciliates the current debate about the participation of the Wnt pathways in axon pathfinding. We then identify the transcription factor (TF) Zic2 as the regulator of this switch and describe the entire set of genes regulated by it. Also, although previous genome-wide approaches have not retrieved the binding motif for this TF, we report here a de novo Zic2 binding motif that is located in promoter and intragenic regions. In addition, we find that the tyrosine kinase EphB receptor, which is one of the genes induced by Zic2, interferes with the Wnt pathway by phosphorylating betacatenin at the growth cone and inducing its asymmetric detachment from the membrane to promote axon steering.
2020-11-19 | GSE133492 | GEO
Project description:Organizers are specialized cell populations that orchestrate cell patterning and axon guidance in the developing nervous system. Although non-human models have led to fundamental discoveries about the organization of the nervous system midline by the floor plate, an experimental model of human floor plate would enable broader insights into regulation of human neurodevelopment and midline connectivity. Here, we have developed stem cell-derived organoids resembling human floor plate (hFpO) and assembled them with spinal cord organoids (hSpO) to generate midline assembloids (hMA). We demonstrate that hFpO promote Sonic hedgehog-dependent ventral patterning of human spinal progenitors and Netrin-dependent guidance of human commissural axons, paralleling non-human models. To investigate evolutionary-divergent midline regulators, we profiled the hFpO secretome and identified 27 evolutionarily divergent genes between human and mouse. Utilizing the hMA platform, we targeted these candidates in an arrayed CRISPR knockout screen and reveal that GALNT2, a gene involved in O-linked glycosylation, impairs floor plate-mediated guidance of commissural axons in humans. This novel platform extends prior axon guidance discoveries into human-specific neurobiology with implications for mechanisms of nervous system evolution and neurodevelopmental disorders.
2025-05-31 | GSE268918 | GEO
Project description:Midline Assembloids Reveal Regulators of Human Axon Guidance
| PRJNA1119448 | ENA
Project description:Axon pathfinding is a key step during the formation of neural circuits but however the transcriptional mechanisms regulating its progression remain poorly understood. The binary decision of crossing or avoiding the midline that neurons make during developmente midline that mammalian retinal ganglion cell (RGC) axons take at the optic chiasm has classically represented a robust model to search for novel mechanisms controlling the selection of axonal trajectories. Here, in order to identify new axon pathfinding regulators, we compared the transcriptome and chromatin accessibility profiles of mammalian retinal ganglion cells RGCs projecting ipsilateral (iRGCs) or contralaterally (cRGCs). Overall, our analyses retrieved dozens of new molecules potentially involved in axon pathfinding and uncovered the regulatory logic behind axon trajectories selection.
2022-08-22 | GSE184275 | GEO
Project description:During the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance. Keywords: Mutant Analysis
2006-12-14 | GSE6515 | GEO
Project description:During peripheral nerve (PN) development, unmyelinated axons (nmAs) initially form tight fascicles before being separated and enveloped by non-myelinating Schwann cells (nmSCs), which are essential for maintaining nmA integrity. The mechanism underlying this transition from axon-axon to axon-glia interactions remains unclear. Here, we found that inactivating nmSC-derived SEMA3B or its axonal receptor components in mice led to incomplete nmA separation and envelopment by nmSCs, leading to nmA dysfunction and inducing hyperalgesia and allodynia. Conversely, increasing SEMA3B levels in nmSCs accelerated nmA separation and envelopment. SEMA3B transiently promoted nmA defasciculation accompanied by cell adhesion molecule (CAM) endocytosis, thus facilitating subsequent CAM-mediated nmA-mSC association. Restoring SEMA3B expression post-PN injury promoted nmA-nmSC re-association and alleviated hyperalgesia and allodynia. We propose that SEMA3B-induced CAM turnover facilitates the switch from axon-axon to axon-glia interactions, promoting nmA envelopment by nmSCs, which may be exploited to alleviate PN injury-induced pain by accelerating the restoration of nmA integrity.
2025-04-09 | GSE294160 | GEO
Project description:Precise wiring of the nervous system depends on coordinating the action of conserved families of proteins that direct axons to their appropriate targets. Slit-roundabout repulsion and netrin-deleted in colorectal cancer (DCC) (frazzled) attraction must be tightly regulated to control midline axon guidance in vertebrates and invertebrates, but the mechanism mediating this regulation is poorly defined. Here, we show that the Fra receptor has two genetically separable functions in regulating midline guidance in Drosophila. First, Fra mediates canonical chemoattraction in response to netrin, and, second, it functions independently of netrin to activate commissureless transcription, allowing attraction to be coupled to the down-regulation of repulsion in precrossing commissural axons.
| S-EPMC4078765 | biostudies-literature
Project description:During the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance. Experiment Overall Design: Several mutants and transgenics were analyzed, totalizing 17 distinct conditions. Individual descriptions are included in each microarray. For each condition there are 3 or 4 replicates. The file's name indicates the replicates, e.g., comm.a reflects the replicate a of mutant commissureless. The experiment design covers a range of mutants and transgenics of key axon guidance mutans, in different dosages. The protocol was the standard Affymetrix protocol.
2008-06-15 | E-GEOD-6515 | biostudies-arrayexpress
Project description:RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurologic disease. Developing axons provide a well suited model to study RNA-based regulation, and contain specific subsets of mRNAs that are locally translated and have roles in axon pathfinding. However, the RNA-binding proteins involved in axon pathfinding, and their corresponding mRNA targets, are still largely unknown. Here we find that the RNA-binding protein IMP2 (Igf2bp2) is strikingly enriched in developing axon tracts, including in spinal commissural axons. We used the HITS-CLIP approach to perform a genome-wide identification of RNAs that interact directly with IMP2 in the native context of developing brain. This IMP2 interactome was highly enriched for mRNA targets related to axon guidance. Accordingly, IMP2 knockdown in the developing spinal cord led to strong defects in commissural axon trajectories at the midline intermediate target. These results reveal a highly distinctive axonal enrichment of IMP2, show that it interacts with a network of axon guidance-related mRNAs, and reveal its requirement for normal axon pathfinding during vertebrate development. CLIP-seq
2016-08-02 | E-GEOD-83822 | biostudies-arrayexpress
Project description:SEMA3B switches axon-axon to axon-glia interactions required for unmyelinated axon envelopment and integrity
| PRJNA1248491 | ENA